Link between low-dose environmentally relevant cadmium exposures and asthenozoospermia in a rat model

Abstract

Objective-To define the mechanism(s) underlying an association between asthenozoospermia and elevated blood, seminal plasma and testicular cadmium levels in infertile human males using a rat model of environmentally relevant cadmium exposures.Setting-University medical center andrology research laboratory. Animals-MaleWistar rats (n = 60), documented to be sensitive to the testicular effects of cadmium.Interventions-Rats were given ad libitum access to water supplemented with 14% sucrose and 0, 5, 50 or 100 mg/L cadmium for 1, 4 or 8 weeks being at puberty.Main outcome measure(s)-Testicular cadmium levels were determined by atomic absorption, cauda epididymal sperm motility by visual inspection, and testicular gene expression by DNA microarray hybridization.Results-Chronic, low dose cadmium exposures produced a time-and dose-dependent reduction in sperm motility. Transcription of genes regulated by calcium and expression of L-type voltagedependent calcium channel mRNA splicing variants were altered by cadmium exposure. Expression of calcium binding proteins involved in modulation of sperm motility was unaffected. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Presented at the UCSF-CHE Summit on Environmental Challenges to Reproductive Health and Fertility, UCSF Mission Bay Conference Center, San Francisco, California, January 28-30, 2007. NIH Public Access Conclusions-A causal relationship between elevated testicular cadmium and asthenozoospermia was identified. Aberrrant sperm motility was correlated with altered expression of L-type voltagedependent calcium channel isoforms found on the sperm tail, which regulate calcium and cadmium influx.

The Blood-Testis Barrier and Its Implications for Male Contraception

“…Furthermore, the seminal plasma cadmium level in heavy smokers is also positively associated with male infertility compared with healthy subjects (Wu et al, 2008). In addition, administration of an environmentally relevant and low dose of cadmium to rats was also shown to induce asthenozoospermia (reduced sperm motility and quality), which is associated with infertility (Benoff et al, 2008). These findings, as summarized herein, are significant because they support the notion that the current trend of declining semen quality, such as sperm count and sperm motility among men in industrialized nations, is caused, at least in part, by low-level exposure to environmental toxicants such as cadmium.…”

Adverse Effects of Low Level Heavy Metal Exposure on Male Reproductive Function

“…Chronic exposure of adult rats to low doses of cadmium (1.6 or 7.4 mg/kg for 14 days) significantly depressed sperm concentration, and human chorionic gonadotrophin (hCG)-stimulated serum testosterone (TE) concentration [Laskey et al 1984]. Exposure of rats to cadmium in drinking water (5 mg/L or 50 mg/L for 4 weeks) produced a dosedependent decrease in sperm motility [Benoff et al 2008]. At doses that did not affect most organs, cadmium caused damage to the testes within 24-48 h. Cadmium also has the ability to disrupt the blood-testis barrier (reviewed in [Siu et al 2009a]).…”

Cadmium Concentrations in Blood and Seminal Plasma: Correlations with Sperm Number and Motility in Three Male Populations (Infertility Patients, Artificial Insemination Donors, and Unselected Volunteers)

“…Oral hydration solutions containing 14% sucrose alone or 14% sucrose supplemented with environmentally realistic low doses of cadmium (5 mg/L, 50 mg/L, and 100 mg/L) were prepared as previously described (43). Cadmium levels were verified by atomic absorption prior to animal administration (43).…”

“…Fivewk-old (pubertal) male Wistar Hanover rats (Charles River Laboratories, Wilmington, MA, USA) were given ad libitum access to a nutritionally complete solid diet in combination with deionized water containing 14% sucrose or 14% sucrose supplemented with cadmium as described above. Animal weight and water consumption (by weight over a 24-h period) were determined twice a wk (43). The animals examined in relation to our three human populations were killed after 4 wk and 8 wk of cadmium exposure (43).…”

“…Elevated seminal plasma and testicular cadmium in these subjects could be derived from contaminated food, another major source of environmental cadmium. Other potential sources of environmental exposure include drinking water, cosmetics, herbal remedies, and industrial pollution (42,43). Interpretations of reported data are complicated by the presence of a number of other toxicants.…”